The miR-183/96/182 Cluster Regulates Sensory Innervation, Resident Myeloid Cells and Functions of the Cornea Through Cell type-specific Target Genes

The miR-183/96/182 cluster (miR-183C) is specifically expressed in sensory neurons and immune cells and modulates corneal immune/inflammatory response to bacterial infection. To uncover the roles of miR-183C in corneal homeostasis through its regulation of sensory neurons of the trigeminal ganglia (TG) and innate myeloid cells, we created miR-183C conventional knockout (KO), and sensory nerve-specific (SNS-CKO) and myeloid cell-specific conditional knockout (MS-CKO) mice. We performed 3'RNA sequencing in the TG and corneas of these knockout mice and their wild type (WT)-control littermates. To study specific functions of miR-183C in corneal resident myeloid cells (CRMCs), we isolated Csf1r-EGFP+ CRMCs from conventional KO and MS-CKO and their WT control mice. By comparison of the gene expression profiles of the KO or CKO vs their corresponding WT mice, we identified a series of differentially expressed genes. Bioinformatic analyses uncovered tissue- and/or cell-type-specific target genes of miR-183C. Functional annotation of the target genes revealed functions of miR-183C in TG and CRMCs. Comparative gene expression profiling analysis of RNA-seq data of TG, cornea and CRMCs of male young adult (8-12 weeks old) miR-183C KO, SNS-CKO and MS-CKO and their WT control mice.miR-183/96/182簇（miR-183C）可特异性表达于感觉神经元与免疫细胞，并调控细菌感染诱导的角膜免疫与炎症应答。为阐明miR-183C通过调控三叉神经节（TG）感觉神经元及先天髓系细胞在角膜稳态中发挥的功能，我们构建了miR-183C常规基因敲除（KO）、感觉神经特异性条件性基因敲除（SNS-CKO）以及髓系细胞特异性条件性基因敲除（MS-CKO）三种小鼠模型。我们对上述基因敲除小鼠及其野生型（WT）同窝对照小鼠的三叉神经节与角膜组织进行了3'端RNA测序。为探究miR-183C在角膜驻留髓系细胞（CRMCs）中的特异性功能，我们从常规KO、MS-CKO小鼠及其WT对照小鼠中分离得到Csf1r-EGFP阳性的角膜驻留髓系细胞。通过对比基因敲除或条件性敲除小鼠与其对应WT小鼠的基因表达谱，我们筛选得到一系列差异表达基因。生物信息学分析揭示了miR-183C的组织及/或细胞类型特异性靶基因；对靶基因进行功能注释后，明确了miR-183C在三叉神经节与角膜驻留髓系细胞中的作用。本数据集包含年轻成年雄性（8~12周龄）miR-183C KO、SNS-CKO及MS-CKO小鼠与其WT对照小鼠的三叉神经节、角膜组织及角膜驻留髓系细胞的RNA测序数据，并开展了对应比较基因表达谱分析。